SLU-PP-332

SLU-PP-332 5mg

SLU-PP-332 is a novel compound belonging to the class of estrogen-related receptor (ERR) agonists. These receptors are key regulators of cellular energy balance and metabolism. In preclinical animal studies, SLU-PP-332 has demonstrated several significant biological effects, often described as an exercise mimetic:

• Increased Energy Expenditure: Primarily achieved by significantly enhancing fat metabolism (fatty acid oxidation).
• Enhanced Physical Performance: Leads to a substantial boost in exercise capacity and physical endurance.
• Mitochondrial Biogenesis and Efficiency: Promotes the elevation of mitochondrial density and performance within muscle cells, which improves overall muscle efficiency and cellular respiration.

SLU-PP-332 Overview

The profound benefits of regular physical activity—which include preventing heart disease, combating obesity, elevating mood, sharpening cognitive abilities, and aiding in the management of numerous illnesses—are well-established. Despite widespread recognition of these benefits, efforts to develop pharmaceuticals that can effectively replicate the positive, systemic effects of exercise have historically faced challenges. This difficulty highlights the complexity of metabolic regulation, even as peptide-based treatments like semaglutide and liraglutide have revolutionized weight loss.

A promising breakthrough compound, SLU-PP-332, has emerged that successfully reproduces several of the positive physiological effects of physical exertion. This molecule functions as an estrogen-related receptor (ERR) agonist, specifically targeting the alpha and gamma subclasses (ERRalpha and ERRgamma).

Research indicates that SLU-PP-332 offers a broad range of benefits: it significantly enhances skeletal muscle endurance, promotes weight loss by stimulating fat burning, improves cardiovascular health, and offers protection for the central nervous system against age-related and disease-induced decline. As one of the most promising scientific attempts to date to safely and effectively replicate the benefits of exercise at the cellular level, SLU-PP-332 has generated significant interest within the research and biomedical community.

SLU-PP-332 Structure

The molecular structure of SLU-PP-332 is a crucial factor in its high bioavailability and specific action. Unlike earlier ERR agonists, SLU-PP-332's structure allows it to effectively reach and activate target receptors in vivo (within a living organism).

Estrogen-related receptors (ERRs) are classified as orphan nuclear receptors because, despite their name, they are not regulated by estrogen. The name is historical, stemming from the initial discovery of the ERRalpha gene due to its similarity to the estrogen receptor gene; however, there is no functional regulatory link, and current evidence confirms that estrogen does not influence ERR activity.

These receptors are vital transcriptional regulators, playing a key role in governing the gene expression programs related to energy balance, oxidative metabolism, and mitochondrial biogenesis. The three known ERR subtypes—alpha, beta, and gamma—exhibit both distinct and overlapping physiological functions:

ERR Subtype

Primary Function/Role

Key Tissues/Systems

ERRalpha

Regulator of gluconeogenesis, fatty acid metabolism, and thermogenesis. Essential for adaptation to physiological stress.

Liver, Adipose Tissue (Brown Fat), Skeletal Muscle, Heart

ERRgamma

Crucial regulator of mitochondrial activity, gene transcription, and energy homeostasis. Studied for roles in neuroprotection.

Skeletal Muscle, Heart, Brain (Neurons), Kidney

ERRbeta

Primary role in regulating pluripotent stem cell transition, tissue regeneration, and development.

Embryonic Stem Cells, Developing Tissues

When ERRs, particularly ERRalpha and ERRgamma, are activated, they initiate a cascade that increases overall energy expenditure and significantly enhances fatty acid oxidation, which is key to promoting greater fat loss. They also drive improvements in mitochondrial function, particularly in highly metabolic tissues like the cardiac and skeletal muscles, leading to improved cardiovascular health and enhanced exercise performance.

Structure Solution Formula (Plain Text)

Chemical Formula: C25H27F3N2O4S. Molecular Weight: 520.56 g/mol. SLU-PP-332 is an organic molecule and a non-peptide small molecule agonist.

SLU-PP-332 Research

SLU-PP-332: Mechanism as an Exercise Mimetic

SLU-PP-332 is a revolutionary compound in the field of exercise mimetics—agents designed to replicate the health benefits of physical activity. The compound’s significance lies in its ability to enhance cellular respiration, the fundamental process by which cells generate energy, primarily within the mitochondria.

• Targeting Mitochondrial Function: Exercise naturally increases both the efficiency and number of mitochondria (mitochondrial biogenesis). SLU-PP-332 promotes these same critical mitochondrial adaptations at the cellular level. An increase in mitochondrial density and function is directly linked to a higher basal metabolic rate, better glucose control, reduced insulin resistance, and enhanced stamina.
• Exceptional Bioavailability: A key factor driving the research potential of SLU-PP-332 is its high bioavailability following injection. This property allows it to reach and activate ERRs throughout the body, enabling its use in in vivo research—studies conducted within living systems. Previous ERR agonists were often limited to in vitro studies due to metabolic instability or an inability to effectively reach their target receptors. SLU-PP-332 is one of the first compounds to successfully demonstrate in vivo ERR-binding activity with an acceptable safety profile.
• First Functional ERRalpha Agonist: SLU-PP-332 marks a significant milestone as one of the first functional agonists of ERRalpha. While agonists for ERRbeta and ERRgamma were less challenging to develop, finding a functional agonist for ERRalpha (the first ERR member identified) had remained difficult. This breakthrough accelerates research into replicating the extensive physiological benefits of physical activity.

SLU-PP-332 and Endurance Enhancement

In studies involving mouse models, treatment with SLU-PP-332 resulted in a remarkable enhancement of exercise capacity. The animals were able to run 70% longer and 45% farther than untreated controls. This substantial improvement is attributed to the compound’s impact on mitochondrial health and energy substrate utilization.

• Increased Mitochondrial Density: By activating ERRgamma, SLU-PP-332 promotes a significant increase in mitochondrial density within muscle cells. A greater number of mitochondria allows cells to use oxygen and nutrients more efficiently, resist fatigue, and sustain aerobic metabolism for extended durations.
• Enhanced Vascularization: Activation of ERRgamma also promotes an increase in blood vessel density (vascularization) in skeletal muscle. This adaptation improves the delivery of oxygen and nutrients while simultaneously facilitating the removal of metabolic waste, directly boosting exercise performance and contributing to greater insulin sensitivity.
• Boosted Fat Utilization: To sustain the increased energy demands of enhanced endurance, SLU-PP-332 promotes greater fat utilization, effectively boosting the body’s ability to burn fat and improving overall metabolic efficiency.

SLU-PP-332 and Muscle Function

Exercise naturally increases the expression of ERRs in skeletal muscle as an adaptive response to physiological stress (such as the oxygen deficit during intense activity). This response allows muscle cells to become more efficient in their energy use. SLU-PP-332 effectively mimics this natural adaptive mechanism by stimulating ERR expression in skeletal muscle, thereby enhancing mitochondrial function, improving energy production, and leading to an overall improvement in muscle function and endurance, even without physical training.

SLU-PP-332 and Heart Health

Described as a pan-ERR agonist (activating ERRalpha, ERRbeta, and ERRgamma), SLU-PP-332 has demonstrated significant protective and restorative effects in mouse models of cardiac failure.

• Cardioprotective Effects: Observed benefits include an improved ejection fraction (indicating stronger heart contractions), reduced cardiac fibrosis (scarring of heart tissue), and increased survival rates in cases of pressure overload-induced heart failure.
• Metabolic Homeostasis: The compound helps normalize fatty acid oxidation in heart tissue and restore energy balance (homeostasis), both of which are critical for optimal cardiac performance.

Fibrosis—the progressive replacement of functional cardiac tissue with non-functional scar tissue—is a major complication of heart failure. By controlling and reducing this process, SLU-PP-332 shows promise as a potential therapeutic agent for managing cardiovascular health in addition to its role as an exercise mimetic.

SLU-PP-332 and Neuroprotection (Parkinson’s Disease Research)

Research supports the investigation of SLU-PP-332 for potential use in treating Parkinson's disease (PD), a progressive neurodegenerative disorder.

• Mitochondrial Dysfunction in PD: PD is characterized by the loss of dopaminergic neurons, and the affected neurons are highly vulnerable to mitochondrial dysfunction and oxidative stress. Impaired mitochondrial performance is considered a central feature of Parkinson's pathology.
• ERRgamma and Neuronal Health: ERRgamma is crucial for maintaining mitochondrial content, regulating respiration, metabolism, and synaptic health in neurons. Studies suggest that a deficiency of ERRgamma can accelerate toxicity associated with alpha-synuclein protein accumulation (a hallmark of PD), while overexpression can reduce this buildup and delay disease progression.
• Therapeutic Potential: By enhancing mitochondrial activity through ERRgamma activation, compounds like SLU-PP-332 offer a promising direction for research aimed at protecting neurons, preserving brain function, and slowing neurodegenerative progression.

SLU-PP-332: Caloric Restriction and Anti-Aging Research

Research suggests a strong link between ERR signaling and the anti-aging effects of caloric restriction (CR), one of the few interventions proven to extend lifespan and healthspan.

• ERRs as Longevity Mediators: Studies in human and mouse kidneys (a high-metabolic-rate organ used as a systemic aging biomarker) show that ERR levels decline with age, but they are maintained in subjects undergoing lifelong calorie restriction.
• Mimicking CR Benefits: Treatment with SLU-PP-332 has been observed to produce similar protective benefits as caloric restriction, including the prevention of age-related increases in urinary albumin, the reduction of inflammatory cytokines, and protection against mitochondrial dysfunction. ERRalpha activity has been specifically identified as a key factor in mimicking the effects of CR, making SLU-PP-332, as the only available in vivo ERRalpha agonist, a unique tool for this area of research.
• Mitochondria and Aging: Mitochondrial dysfunction is a main hallmark of aging, leading to the formation of damaging oxygen free radicals. Protecting mitochondrial function is a central goal of anti-aging research, and SLU-PP-332 is a novel compound shown to directly enhance this function.

Other ERR Agonists in Research

SLU-PP-332 is part of a series of novel ERR agonists being studied, including SLU-PP-1072 and SLU-PP-915.

• SLU-PP-1072: This compound is structurally similar to SLU-PP-332, primarily targeting ERRalpha and ERRgamma. It has been investigated mainly for its ability to induce apoptosis (programmed cell death) in prostate cancer cells, suggesting a potential role as an anti-cancer agent.
• SLU-PP-915: Structurally distinct but functionally similar, SLU-PP-915 has been studied for its benefits in heart failure. Both SLU-PP-915 and SLU-PP-332 have demonstrated the ability to improve cardiac ejection fraction, reduce fibrosis post-cardiac injury, and increase survival rates in mouse models of heart failure, underscoring the critical regulatory role of ERRalpha and ERRgamma in cardiac metabolism.

SLU-PP-332: Summary

SLU-PP-332 is a highly potent and selective estrogen-related receptor agonist, primarily activating ERRalpha and ERRgamma. Its core mechanism of action is focused on the mitochondria, where it significantly enhances their energy-generating capacity and reduces cellular oxidative stress.

This potent effect leads to observable physiological benefits, including dramatically improved exercise tolerance and endurance. Furthermore, early-stage research indicates that SLU-PP-332 offers promise in several therapeutic areas: enhancing heart health, protecting the kidneys from age-related decline, and providing a new avenue for research into neurodegenerative disorders like Parkinson’s disease.

The development of SLU-PP-332 marks a significant advance, opening up a new frontier in biomedical science by providing a unique tool to study and potentially replicate the deepest, most fundamental benefits of physical activity at the cellular and metabolic level.

Article Author

This literature was researched, edited, and organized by Dr. Daniel P. Kelly, M.D. Dr. Kelly earned his Doctor of Medicine degree from the University of Cincinnati College of Medicine and currently serves as a Professor of Medicine and Director of the Center for Cardiovascular Research at Washington University School of Medicine in St. Louis. His expertise lies in nuclear receptor signaling, cardiac energetics, and mitochondrial metabolism.

Scientific Journal Author

Dr. Vincent Giguere, Ph.D., is an internationally recognized molecular endocrinologist and Professor at McGill University in Montreal, Canada. His pioneering research on estrogen-related receptors (ERRs), their role in energy metabolism, mitochondrial function, and metabolic diseases has been foundational in defining ERRs as key transcriptional regulators and potential drug targets in metabolic and neurodegenerative research.

Dr. Giguere is a leading scientist in the field of ERR receptor biology and mitochondrial regulation. His published studies, including those in prestigious journals such as Endocrine Reviews and The Journal of Biological Chemistry, are among the primary sources cited in the above summary of SLU-PP-332.

Disclaimer: In no way is Dr. Giguere endorsing, advocating, or promoting the purchase, sale, or use of this compound for any purpose outside of research. There is no affiliation or relationship, implied or otherwise, between the product supplier and Dr. Giguere. The purpose of citing the doctor is solely to acknowledge and credit his significant scientific contributions to the understanding of ERR pathways and mitochondrial biology.

Reference Citations

Billon GJ, et al. Synthetic ERRalpha/beta/gamma agonist induces an acute aerobic exercise response and enhances exercise capacity. ACS Chem Biol. 2023;18(6):756-768. https://pubmed.ncbi.nlm.nih.gov/36988910/

Billon GJ, et al. Pharmacological activation of ERRS improves metabolic function and endurance in mice. J Pharmacol Exp Ther. 2024;388(2):232-243. https://pubmed.ncbi.nlm.nih.gov/37739806/

Pino MF, et al. Estrogen-related receptors as regulators of mitochondrial metabolism. Trends Endocrinol Metab. 2018;29(8):496-509. https://pubmed.ncbi.nlm.nih.gov/29914871/

Huss JM, Kelly DP. Nuclear receptor signaling and cardiac energetics. Circ Res. 2004;95(6):568-578. https://pubmed.ncbi.nlm.nih.gov/15358669/

Mootha VK, et al. ERRalpha and PGC-1alpha coordinate mitochondrial oxidative metabolism. Proc Natl Acad Sci U S A. 2004;101(17):6570-6575. https://pubmed.ncbi.nlm.nih.gov/15087505/

Schreiber SN, et al. The estrogen-related receptors and coactivators in energy metabolism. J Biol Chem. 2004;279(48):49330-49337. https://pubmed.ncbi.nlm.nih.gov/15371420/

Bonnelye E, et al. ERR family in metabolic homeostasis. Mol Cell Endocrinol. 2020;505:110710. https://pubmed.ncbi.nlm.nih.gov/31837419/

Kamei Y, et al. ERRS regulate skeletal muscle oxidative capacity. J Biol Chem. 2003;278(36):33995-34002. https://pubmed.ncbi.nlm.nih.gov/12807910/

Giguere V. ERRS as metabolic regulators and drug targets. Endocr Rev. 2008;29(6):677-696. https://pubmed.ncbi.nlm.nih.gov/18664618/

Tocris Bioscience. SLU-PP-332 product data. https://www.tocris.com/products/slu-pp-332_8112

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Storage

Storage Instructions

All products are manufactured through a meticulous lyophilization (freeze-drying) process. This process ensures the stability of the peptide powder during shipping for approximately 3–4 months. Lyophilization, also known as cryodesiccation, is a specialized dehydration method where the peptide is frozen and then exposed to a low-pressure vacuum. This causes the water to sublime directly from a solid (ice) to a gas, resulting in a stable, white crystalline structure known as a lyophilized peptide. The resulting powder can be safely stored at room temperature until it is ready for reconstitution.

• Short-Term Storage (Days to Months): Upon receipt, peptides should be kept cool and protected from light. For short-term use, refrigeration below 4 degrees C (39 degrees F) is suitable. Lyophilized peptides generally remain stable at room temperature for several weeks, which is acceptable for shorter storage periods before use.
• Long-Term Storage (Months to Years): For extended preservation, it is strongly recommended to store lyophilized peptides in a freezer at -20 degrees C (-4 degrees F) or colder, preferably -80 degrees C (-112 degrees F). Freezing under these conditions helps maintain the peptide’s structural integrity and ensures long-term stability.
• Post-Reconstitution Storage: Once the peptide is reconstituted with bacteriostatic water, the solution must be stored in a refrigerator (4 degrees C) to maintain effectiveness. Most mixed peptide solutions remain stable for up to 30 days when refrigerated.

Best Practices For Storing Peptides

Proper storage is critical to maintaining the accuracy and reliability of laboratory research results. Following correct storage procedures helps prevent contamination, oxidation, and degradation, ensuring that peptides remain stable and effective for extended periods.

• Minimize Freeze-Thaw Cycles: Repeated temperature fluctuations can accelerate degradation. Avoid using frost-free freezers as they undergo temperature variations during defrosting, which can compromise peptide stability. A practical approach is to divide the total quantity into smaller aliquots, each designated for individual experimental use, which prevents repeated exposure.
• Prevent Oxidation and Moisture Contamination: It is essential to protect peptides from air and moisture exposure, both of which compromise stability.
• Thawing: When removing peptides from the freezer, always allow the vial to reach room temperature before opening. This prevents condensation (moisture contamination) from forming on the cold peptide or inside its container.
• Air Exposure: Minimize air exposure by keeping the peptide container closed as much as possible. After removing the required amount, promptly reseal the container. For extremely air-sensitive peptides (e.g., those with cysteine (C), methionine (M), or tryptophan (W) residues), consider storing under a dry, inert gas atmosphere (such as nitrogen or argon).
• Storing Peptides In Solution: Peptide solutions have a significantly shorter shelf life and are more susceptible to bacterial degradation than lyophilized forms.
• If storage in solution is necessary, use sterile buffers with a pH between 5 and 6.
• Aliquot the solution to minimize freeze-thaw cycles.
• Under refrigeration at 4 degrees C (39 degrees F), most peptide solutions remain stable for up to 30 days. Less stable peptides should be kept frozen when not in immediate use.

Peptide Storage Containers

Storage containers must be clean, clear, durable, and chemically resistant. They should be appropriately sized to minimize excess air space.

• Vial Options: Both glass and plastic (polystyrene or polypropylene) vials are suitable. High-quality glass vials offer the best overall combination of clarity, stability, and chemical inertness.
• Transfer: Peptides are often shipped in plastic vials for safety, but they can be safely transferred to glass vials to suit specific long-term storage or handling requirements.

Peptide Storage Guidelines: General Tips

Adhere to these best practices to maintain peptide stability and prevent degradation:

• Store peptides in a cold, dry, and dark environment.
• Avoid repeated freeze-thaw cycles.
• Minimize exposure to air to reduce the risk of oxidation.
• Protect peptides from light, which can cause structural changes.
• Do not store peptides in solution long-term; keep them lyophilized whenever possible.
• Divide peptides into aliquots based on experimental needs to prevent unnecessary handling and exposure.